Mary Ann Moon

Insulin resistance appears to be associated with a nearly threefold increased risk for ischemic stroke, independently of established cardiovascular risk factors such as diabetes, obesity, and the metabolic syndrome, according to a prospective cohort study reported in the October issue of the Archives of Neurology.

If this conclusion is confirmed in further studies, “insulin resistance may [become] a novel therapeutic target for stroke prevention,” said Dr. Tatjana Rundek of the department of neurology at the University of Miami and her associates.

Although insulin resistance is “a pivotal pathophysiologic contributor” to cardiovascular disease, its role in ischemic stroke “is still a matter of debate,” the investigators noted.

They used data from the Northern Manhattan Study, a prospective, population-based cohort study of stroke, to examine the issue. The study population comprised 1,509 older adults residing in a multiethnic urban community who were enrolled between 1993 and 2001 and followed for a mean of 8.5 years.

The study subjects had no stroke, MI, or diabetes at baseline. The mean age was 68 years. About 60% were Hispanic, 20% were black, and 20% were white.

In all, 23% of the men and 26% of the women were estimated to have insulin resistance, as measured indirectly by the homeostasis model assessment (HOMA).

Overall, 180 subjects had one or more symptomatic vascular events, including 46 ischemic strokes, 45 MIs, and 121 vascular deaths.

Study subjects with insulin resistance – those in the highest quartile of HOMA scores – showed a significant 2.8-fold higher risk of ischemic stroke than did those with lower HOMA scores. This association was stronger in men than in women, and it persisted when the data were adjusted to control for sociodemographic factors, the presence or absence of the metabolic syndrome, and vascular risk factors.

In contrast, neither the association between insulin resistance and MI nor the association between insulin resistance and vascular death were significant, Dr. Rundek and her colleagues said (Arch. Neurol. 2010;67:1195-200).

The findings should not be considered conclusive, since replication “with larger data sets and more end points” is still necessary, they added.

If this association is confirmed, certain classes of drugs that improve insulin sensitivity and beta-cell function may prove helpful in preventing stroke.

The study results also “suggest that metabolic syndrome may not capture all the vascular risk associated with insulin resistance, raising the possibility that other pathways affected by insulin resistance, such as inflammation, may be important,” the researchers said.

Support for the study included the Goddess Fund for Stroke Research in Women, the U.S. National Institute of Neurological Disorders and Stroke, the American Heart Association, and Columbia University. The investigators reported no financial conflicts of interest.

Insulin resistance appears to be associated with a nearly threefold increased risk for ischemic stroke, independently of established cardiovascular risk factors such as diabetes, obesity, and the metabolic syndrome, according to a prospective cohort study reported in the October issue of the Archives of Neurology.

If this conclusion is confirmed in further studies, “insulin resistance may [become] a novel therapeutic target for stroke prevention,” said Dr. Tatjana Rundek of the department of neurology at the University of Miami and her associates.

Although insulin resistance is “a pivotal pathophysiologic contributor” to cardiovascular disease, its role in ischemic stroke “is still a matter of debate,” the investigators noted.

They used data from the Northern Manhattan Study, a prospective, population-based cohort study of stroke, to examine the issue. The study population comprised 1,509 older adults residing in a multiethnic urban community who were enrolled between 1993 and 2001 and followed for a mean of 8.5 years.

The study subjects had no stroke, MI, or diabetes at baseline. The mean age was 68 years. About 60% were Hispanic, 20% were black, and 20% were white.

In all, 23% of the men and 26% of the women were estimated to have insulin resistance, as measured indirectly by the homeostasis model assessment (HOMA).

Overall, 180 subjects had one or more symptomatic vascular events, including 46 ischemic strokes, 45 MIs, and 121 vascular deaths.

Study subjects with insulin resistance – those in the highest quartile of HOMA scores – showed a significant 2.8-fold higher risk of ischemic stroke than did those with lower HOMA scores. This association was stronger in men than in women, and it persisted when the data were adjusted to control for sociodemographic factors, the presence or absence of the metabolic syndrome, and vascular risk factors.

In contrast, neither the association between insulin resistance and MI nor the association between insulin resistance and vascular death were significant, Dr. Rundek and her colleagues said (Arch. Neurol. 2010;67:1195-200).

The findings should not be considered conclusive, since replication “with larger data sets and more end points” is still necessary, they added.

If this association is confirmed, certain classes of drugs that improve insulin sensitivity and beta-cell function may prove helpful in preventing stroke.

The study results also “suggest that metabolic syndrome may not capture all the vascular risk associated with insulin resistance, raising the possibility that other pathways affected by insulin resistance, such as inflammation, may be important,” the researchers said.

Support for the study included the Goddess Fund for Stroke Research in Women, the U.S. National Institute of Neurological Disorders and Stroke, the American Heart Association, and Columbia University. The investigators reported no financial conflicts of interest.

Insulin resistance appears to be associated with a nearly threefold increased risk for ischemic stroke, independently of established cardiovascular risk factors such as diabetes, obesity, and the metabolic syndrome, according to a prospective cohort study reported in the October issue of the Archives of Neurology.

If this conclusion is confirmed in further studies, “insulin resistance may [become] a novel therapeutic target for stroke prevention,” said Dr. Tatjana Rundek of the department of neurology at the University of Miami and her associates.

Although insulin resistance is “a pivotal pathophysiologic contributor” to cardiovascular disease, its role in ischemic stroke “is still a matter of debate,” the investigators noted.

They used data from the Northern Manhattan Study, a prospective, population-based cohort study of stroke, to examine the issue. The study population comprised 1,509 older adults residing in a multiethnic urban community who were enrolled between 1993 and 2001 and followed for a mean of 8.5 years.

The study subjects had no stroke, MI, or diabetes at baseline. The mean age was 68 years. About 60% were Hispanic, 20% were black, and 20% were white.

In all, 23% of the men and 26% of the women were estimated to have insulin resistance, as measured indirectly by the homeostasis model assessment (HOMA).

Overall, 180 subjects had one or more symptomatic vascular events, including 46 ischemic strokes, 45 MIs, and 121 vascular deaths.

Study subjects with insulin resistance – those in the highest quartile of HOMA scores – showed a significant 2.8-fold higher risk of ischemic stroke than did those with lower HOMA scores. This association was stronger in men than in women, and it persisted when the data were adjusted to control for sociodemographic factors, the presence or absence of the metabolic syndrome, and vascular risk factors.

In contrast, neither the association between insulin resistance and MI nor the association between insulin resistance and vascular death were significant, Dr. Rundek and her colleagues said (Arch. Neurol. 2010;67:1195-200).

The findings should not be considered conclusive, since replication “with larger data sets and more end points” is still necessary, they added.

If this association is confirmed, certain classes of drugs that improve insulin sensitivity and beta-cell function may prove helpful in preventing stroke.

The study results also “suggest that metabolic syndrome may not capture all the vascular risk associated with insulin resistance, raising the possibility that other pathways affected by insulin resistance, such as inflammation, may be important,” the researchers said.

Support for the study included the Goddess Fund for Stroke Research in Women, the U.S. National Institute of Neurological Disorders and Stroke, the American Heart Association, and Columbia University. The investigators reported no financial conflicts of interest.

Carotid artery stenting carries higher intermediate- and long-term risks than does carotid endarterectomy, not just higher periprocedural risks, according to the largest and most comprehensive metaanalysis of available evidence from randomized trials to date.

The safety and efficacy of carotid stenting as an alternative to endarterectomy are controversial. Several studies have indicated that stenting is more likely to cause periprocedural stroke, but the data on longer-term outcomes are limited, said Dr. Sripal Bangalore of New York University, New York, and his associates.

In their Oct. 11 online report in the Archives of Neurology, the investigators examined 13 randomized controlled trials that reported outcomes at 30 days or later and included 3,754 patients assigned to stenting and 3,723 to endarterectomy. The mean follow-up in the trials was 2.7 years.

In the short term, stenting was associated with a 31% increase in the risk of periprocedural death, MI, or stroke, compared with endarterectomy. The absolute rates of periprocedural death, MI, or stroke were 5.7% with stenting and 4.7% with endarterectomy, they said.

In the long term, the risk for that composite outcome plus later ipsilateral stroke or death was 19% higher following stenting than it was after endarterectomy. In comparison with endarterectomy, stenting carried a 38% higher risk of the composite outcome of periprocedural stroke or death plus later ipsilateral stroke, a 24% higher risk of the composite outcome of death or stroke, and a 48% increased risk of any stroke.

These increases in long-term risks were consistent across several subgroups of patients: symptomatic or asymptomatic, low risk or high risk, American or non-American, and regardless of whether an embolic protection device was used, Dr. Bangalore and his colleagues wrote (Arch. Neurol. 2010 Oct. 11 [doi:10.1001/archneurol.2010.262]).

However, the rate of periprocedural MI was significantly lower with carotid stenting (0.3%) than with endarterectomy (1.2%). And stenting was associated with an 85% reduction in the risk of cranial nerve injury, all of which occurred in the periprocedural period.

“Our results suggest that the [already known] periprocedural increased risk of carotid artery stenting continues to be seen in the intermediate- to long-term periods as well,” the investigators wrote.

Despite these findings, carotid stenting remains a useful alternative, given that it is less invasive and entails a shorter recovery period than endarterectomy and that it would be beneficial for patients who are poor surgical candidates or at high risk for periprocedural MI. Therefore, “there is an urgent need” to develop the means to select patients who have a low risk of complications with stenting, the researchers added.

One of Dr. Bangalore’s associates reported receiving research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis, and the Medicines Company.

Carotid artery stenting carries higher intermediate- and long-term risks than does carotid endarterectomy, not just higher periprocedural risks, according to the largest and most comprehensive metaanalysis of available evidence from randomized trials to date.

The safety and efficacy of carotid stenting as an alternative to endarterectomy are controversial. Several studies have indicated that stenting is more likely to cause periprocedural stroke, but the data on longer-term outcomes are limited, said Dr. Sripal Bangalore of New York University, New York, and his associates.

In their Oct. 11 online report in the Archives of Neurology, the investigators examined 13 randomized controlled trials that reported outcomes at 30 days or later and included 3,754 patients assigned to stenting and 3,723 to endarterectomy. The mean follow-up in the trials was 2.7 years.

In the short term, stenting was associated with a 31% increase in the risk of periprocedural death, MI, or stroke, compared with endarterectomy. The absolute rates of periprocedural death, MI, or stroke were 5.7% with stenting and 4.7% with endarterectomy, they said.

In the long term, the risk for that composite outcome plus later ipsilateral stroke or death was 19% higher following stenting than it was after endarterectomy. In comparison with endarterectomy, stenting carried a 38% higher risk of the composite outcome of periprocedural stroke or death plus later ipsilateral stroke, a 24% higher risk of the composite outcome of death or stroke, and a 48% increased risk of any stroke.

These increases in long-term risks were consistent across several subgroups of patients: symptomatic or asymptomatic, low risk or high risk, American or non-American, and regardless of whether an embolic protection device was used, Dr. Bangalore and his colleagues wrote (Arch. Neurol. 2010 Oct. 11 [doi:10.1001/archneurol.2010.262]).

However, the rate of periprocedural MI was significantly lower with carotid stenting (0.3%) than with endarterectomy (1.2%). And stenting was associated with an 85% reduction in the risk of cranial nerve injury, all of which occurred in the periprocedural period.

“Our results suggest that the [already known] periprocedural increased risk of carotid artery stenting continues to be seen in the intermediate- to long-term periods as well,” the investigators wrote.

Despite these findings, carotid stenting remains a useful alternative, given that it is less invasive and entails a shorter recovery period than endarterectomy and that it would be beneficial for patients who are poor surgical candidates or at high risk for periprocedural MI. Therefore, “there is an urgent need” to develop the means to select patients who have a low risk of complications with stenting, the researchers added.

One of Dr. Bangalore’s associates reported receiving research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis, and the Medicines Company.

Carotid artery stenting carries higher intermediate- and long-term risks than does carotid endarterectomy, not just higher periprocedural risks, according to the largest and most comprehensive metaanalysis of available evidence from randomized trials to date.

The safety and efficacy of carotid stenting as an alternative to endarterectomy are controversial. Several studies have indicated that stenting is more likely to cause periprocedural stroke, but the data on longer-term outcomes are limited, said Dr. Sripal Bangalore of New York University, New York, and his associates.

In their Oct. 11 online report in the Archives of Neurology, the investigators examined 13 randomized controlled trials that reported outcomes at 30 days or later and included 3,754 patients assigned to stenting and 3,723 to endarterectomy. The mean follow-up in the trials was 2.7 years.

In the short term, stenting was associated with a 31% increase in the risk of periprocedural death, MI, or stroke, compared with endarterectomy. The absolute rates of periprocedural death, MI, or stroke were 5.7% with stenting and 4.7% with endarterectomy, they said.

In the long term, the risk for that composite outcome plus later ipsilateral stroke or death was 19% higher following stenting than it was after endarterectomy. In comparison with endarterectomy, stenting carried a 38% higher risk of the composite outcome of periprocedural stroke or death plus later ipsilateral stroke, a 24% higher risk of the composite outcome of death or stroke, and a 48% increased risk of any stroke.

These increases in long-term risks were consistent across several subgroups of patients: symptomatic or asymptomatic, low risk or high risk, American or non-American, and regardless of whether an embolic protection device was used, Dr. Bangalore and his colleagues wrote (Arch. Neurol. 2010 Oct. 11 [doi:10.1001/archneurol.2010.262]).

However, the rate of periprocedural MI was significantly lower with carotid stenting (0.3%) than with endarterectomy (1.2%). And stenting was associated with an 85% reduction in the risk of cranial nerve injury, all of which occurred in the periprocedural period.

“Our results suggest that the [already known] periprocedural increased risk of carotid artery stenting continues to be seen in the intermediate- to long-term periods as well,” the investigators wrote.

Despite these findings, carotid stenting remains a useful alternative, given that it is less invasive and entails a shorter recovery period than endarterectomy and that it would be beneficial for patients who are poor surgical candidates or at high risk for periprocedural MI. Therefore, “there is an urgent need” to develop the means to select patients who have a low risk of complications with stenting, the researchers added.

One of Dr. Bangalore’s associates reported receiving research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis, and the Medicines Company.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Severe hypoglycemia in patients with long-standing type 2 diabetes is strongly associated with a broad range of adverse outcomes, including death from cardiovascular and noncardiovascular causes, according to a report in the Oct. 7 issue of the New England Journal of Medicine.

However, there is no close temporal relationship between episodes of severe hypoglycemia and such adverse events, nor is there a dose-response relationship in which more frequent hypoglycemic episodes carry increasingly higher risks.

“Although our findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of clinical outcomes. In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” said Dr. Sophia Zoungas of the George Institute for International Health, University of Sydney, and her associates in the ADVANCE clinical trial.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation assessed 11,140 patients aged 55 years and older who had type 2 diabetes and were followed at 215 medical centers in 20 countries for a median of 5 years.

The study subjects were randomly assigned to receive either intensive or standard glucose-lowering therapy. A total of 231 (approximately 2%) reported experiencing 299 severe hypoglycemic events: 150 (2.7%) receiving intensive therapy reported 195 events and 81 (1.5%) receiving standard therapy reported 104 events.

Major macrovascular or microvascular events occurred in 2,125 subjects, 87 of whom reported severe hypoglycemic events. And 1,031 subjects died, 45 of whom reported severe hypoglycemic events.

Nearly 17% of subjects who reported severe hypoglycemia subsequently had a major macrovascular event, 12% had a subsequent major microvascular event, and 20% died. In contrast, the corresponding proportions for subjects who did not report severe hypoglycemia were 10%, 10%, and 9%, respectively, the investigators said (N. Engl. J. Med. 2010;363:1410-8).

In addition, risks for disorders of the respiratory system, digestive system, and skin were elevated in patients who had severe hypoglycemic episodes, compared with those who did not.

Hypoglycemia conceivably could have contributed to both cardiovascular and noncardiovascular disorders and death by means of sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis, inflammation, or vasoconstriction. However, it is also possible that hypoglycemia might only have reflected the effects of “coexisting conditions and unmeasured or incompletely quantified confounding variables,” making it a marker rather than a direct cause of adverse outcomes, Dr. Zoungas and her colleagues noted.

The latter scenario appears to be more likely, given that no temporal relationship and no dose-response relationship were found between hypoglycemic events and adverse outcomes, they added.

The ADVANCE study was supported by Servier and the National Health and Medical Research Council of Australia. Dr. Zoungas and her associates reported ties to Servier, Norvo Nordisk, Eli Lilly & Co., Sanofi-Aventis, Takeda Pharmaceutical Co., Pfizer, Roche, Amgen Inc., AstraZeneca, GlaxoSmithKline, Tanabe, Merck Sharpe and Dolhm, Abbott Laboratories, Johnson & Johnson, and Merck Schering Plough.

Pluripotent stem cells, derived from skin fibroblasts of two relatives with familial long-QT syndrome and induced to differentiate into cardiac myocytes, exhibited the electrophysiologic traits of the disorder, showing for the first time that stem cell models “can recapitulate aspects of genetic cardiac diseases,” according to a small study reported in the Oct. 7 issue of the New England Journal of Medicine.

The research findings have far-reaching implications for cardiac research in general, not just for the relatively uncommon long-QT syndrome, including opening the door to in vitro development and testing of new cardiac medications, said Alessandra Moretti, Ph.D., and her associates at the Technical University of Munich.

They obtained skin fibroblasts from an 8-year-old boy when clinical evaluation for attention-deficit/hyperactivity disorder revealed a prolonged QT interval on his electrocardiogram, and subsequent genotyping revealed that he carried a mutation of the KSNQ1 gene that characterizes long-QT syndrome type 1. Skin fibroblasts also were obtained from the patient’s father, who also carried the same mutation.

The researchers grew pluripotent stem cell colonies from these cells, as well as from the cells of two healthy control subjects. The cells were induced to differentiate into the cardiac lineages. Then spontaneously beating cells were subjected to pacing, then separated into three distinct types of action potentials corresponding to “ventricular,” “atrial,” and “nodal” myocytes.

When compared with myocytes derived from the control subjects, the patients’ myocytes showed prolongation of the action potential, altered IKs activation and deactivation, and an abnormal response to catecholamine stimulation – all of which are characteristic of the cardiac abnormalities in long-QT syndrome. Further characterization of the KSNQ1 mutation showed that “a dominant negative trafficking defect” was associated with the 70%-80% reduction in IKs current and altered properties governing channel activation and deactivation.

The investigators then assessed the effects of adrenergic stimulation by exposing the beating myocytes to isoproterenol. This shortened the action potential of the myocytes from the control subjects but lengthened that of the myocytes from affected patients, “exacerbating the long-QT syndrome type 1 phenotype and increasing the risk of arrhythmic events” in the cells.

Pretreating the myocytes by exposing them to the beta-blocker propranolol induced a protective effect, much as beta-blocker therapy protects affected patients from the effects of abnormally prolonged ventricular repolarization phase: a propensity for polymorphic ventricular tachycardia and sudden cardiac death.

“Our findings suggest that there may be alternative approaches to the development of candidate drugs” to treat this and other genetic cardiac disorders, Dr. Moretti and her colleagues said (N. Engl. J. Med. 2010;363:1397-409).

In particular, “the observed protective effects of beta-blockade show that it is possible to investigate the therapeutic action of medications for treating human cardiac disease in vitro with the use of patient-specific cells. This approach is particularly attractive because of the pluripotent nature of these cells and the potentially unlimited number of induced cardiomyocytes available for high-throughput drug development,” they noted.

Until now, research on the pathogenesis of the long-QT syndrome has relied primarily on genetic animal models. But because of the differences among species in the chemical channels that generate cardiac repolarizing currents, “none of the available [animal] models of the long-QT syndrome fully emulate the human disease phenotype.”

This study thus demonstrates “the importance of alternative systems in which human genetic disorders can be studied in the physiologic and disease-causing contexts on a patient-specific level,” the researchers said.

This work was supported by grants from the European Research Council, the German Research Foundation, and the German Ministry for Education and Research. One of the investigators also reported receiving Deutsche Forschungsgemeinschaft grant support.

Pluripotent stem cells, derived from skin fibroblasts of two relatives with familial long-QT syndrome and induced to differentiate into cardiac myocytes, exhibited the electrophysiologic traits of the disorder, showing for the first time that stem cell models “can recapitulate aspects of genetic cardiac diseases,” according to a small study reported in the Oct. 7 issue of the New England Journal of Medicine.

The research findings have far-reaching implications for cardiac research in general, not just for the relatively uncommon long-QT syndrome, including opening the door to in vitro development and testing of new cardiac medications, said Alessandra Moretti, Ph.D., and her associates at the Technical University of Munich.

They obtained skin fibroblasts from an 8-year-old boy when clinical evaluation for attention-deficit/hyperactivity disorder revealed a prolonged QT interval on his electrocardiogram, and subsequent genotyping revealed that he carried a mutation of the KSNQ1 gene that characterizes long-QT syndrome type 1. Skin fibroblasts also were obtained from the patient’s father, who also carried the same mutation.

The researchers grew pluripotent stem cell colonies from these cells, as well as from the cells of two healthy control subjects. The cells were induced to differentiate into the cardiac lineages. Then spontaneously beating cells were subjected to pacing, then separated into three distinct types of action potentials corresponding to “ventricular,” “atrial,” and “nodal” myocytes.

When compared with myocytes derived from the control subjects, the patients’ myocytes showed prolongation of the action potential, altered IKs activation and deactivation, and an abnormal response to catecholamine stimulation – all of which are characteristic of the cardiac abnormalities in long-QT syndrome. Further characterization of the KSNQ1 mutation showed that “a dominant negative trafficking defect” was associated with the 70%-80% reduction in IKs current and altered properties governing channel activation and deactivation.

The investigators then assessed the effects of adrenergic stimulation by exposing the beating myocytes to isoproterenol. This shortened the action potential of the myocytes from the control subjects but lengthened that of the myocytes from affected patients, “exacerbating the long-QT syndrome type 1 phenotype and increasing the risk of arrhythmic events” in the cells.

Pretreating the myocytes by exposing them to the beta-blocker propranolol induced a protective effect, much as beta-blocker therapy protects affected patients from the effects of abnormally prolonged ventricular repolarization phase: a propensity for polymorphic ventricular tachycardia and sudden cardiac death.

“Our findings suggest that there may be alternative approaches to the development of candidate drugs” to treat this and other genetic cardiac disorders, Dr. Moretti and her colleagues said (N. Engl. J. Med. 2010;363:1397-409).

In particular, “the observed protective effects of beta-blockade show that it is possible to investigate the therapeutic action of medications for treating human cardiac disease in vitro with the use of patient-specific cells. This approach is particularly attractive because of the pluripotent nature of these cells and the potentially unlimited number of induced cardiomyocytes available for high-throughput drug development,” they noted.

Until now, research on the pathogenesis of the long-QT syndrome has relied primarily on genetic animal models. But because of the differences among species in the chemical channels that generate cardiac repolarizing currents, “none of the available [animal] models of the long-QT syndrome fully emulate the human disease phenotype.”

This study thus demonstrates “the importance of alternative systems in which human genetic disorders can be studied in the physiologic and disease-causing contexts on a patient-specific level,” the researchers said.

This work was supported by grants from the European Research Council, the German Research Foundation, and the German Ministry for Education and Research. One of the investigators also reported receiving Deutsche Forschungsgemeinschaft grant support.

Pluripotent stem cells, derived from skin fibroblasts of two relatives with familial long-QT syndrome and induced to differentiate into cardiac myocytes, exhibited the electrophysiologic traits of the disorder, showing for the first time that stem cell models “can recapitulate aspects of genetic cardiac diseases,” according to a small study reported in the Oct. 7 issue of the New England Journal of Medicine.

The research findings have far-reaching implications for cardiac research in general, not just for the relatively uncommon long-QT syndrome, including opening the door to in vitro development and testing of new cardiac medications, said Alessandra Moretti, Ph.D., and her associates at the Technical University of Munich.

They obtained skin fibroblasts from an 8-year-old boy when clinical evaluation for attention-deficit/hyperactivity disorder revealed a prolonged QT interval on his electrocardiogram, and subsequent genotyping revealed that he carried a mutation of the KSNQ1 gene that characterizes long-QT syndrome type 1. Skin fibroblasts also were obtained from the patient’s father, who also carried the same mutation.

The researchers grew pluripotent stem cell colonies from these cells, as well as from the cells of two healthy control subjects. The cells were induced to differentiate into the cardiac lineages. Then spontaneously beating cells were subjected to pacing, then separated into three distinct types of action potentials corresponding to “ventricular,” “atrial,” and “nodal” myocytes.

When compared with myocytes derived from the control subjects, the patients’ myocytes showed prolongation of the action potential, altered IKs activation and deactivation, and an abnormal response to catecholamine stimulation – all of which are characteristic of the cardiac abnormalities in long-QT syndrome. Further characterization of the KSNQ1 mutation showed that “a dominant negative trafficking defect” was associated with the 70%-80% reduction in IKs current and altered properties governing channel activation and deactivation.

The investigators then assessed the effects of adrenergic stimulation by exposing the beating myocytes to isoproterenol. This shortened the action potential of the myocytes from the control subjects but lengthened that of the myocytes from affected patients, “exacerbating the long-QT syndrome type 1 phenotype and increasing the risk of arrhythmic events” in the cells.

Pretreating the myocytes by exposing them to the beta-blocker propranolol induced a protective effect, much as beta-blocker therapy protects affected patients from the effects of abnormally prolonged ventricular repolarization phase: a propensity for polymorphic ventricular tachycardia and sudden cardiac death.

“Our findings suggest that there may be alternative approaches to the development of candidate drugs” to treat this and other genetic cardiac disorders, Dr. Moretti and her colleagues said (N. Engl. J. Med. 2010;363:1397-409).

In particular, “the observed protective effects of beta-blockade show that it is possible to investigate the therapeutic action of medications for treating human cardiac disease in vitro with the use of patient-specific cells. This approach is particularly attractive because of the pluripotent nature of these cells and the potentially unlimited number of induced cardiomyocytes available for high-throughput drug development,” they noted.

Until now, research on the pathogenesis of the long-QT syndrome has relied primarily on genetic animal models. But because of the differences among species in the chemical channels that generate cardiac repolarizing currents, “none of the available [animal] models of the long-QT syndrome fully emulate the human disease phenotype.”

This study thus demonstrates “the importance of alternative systems in which human genetic disorders can be studied in the physiologic and disease-causing contexts on a patient-specific level,” the researchers said.

This work was supported by grants from the European Research Council, the German Research Foundation, and the German Ministry for Education and Research. One of the investigators also reported receiving Deutsche Forschungsgemeinschaft grant support.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

Adding a proton pump inhibitor to dual antiplatelet therapy significantly reduced the risk of gastrointestinal bleeding without raising the risk of cardiovascular events, according to a report published online Oct. 6 in the New England Journal of Medicine.

The finding that PPIs don’t appear to blunt the effect of antiplatelets is reassuring in view of the results of several previous studies that found a possible adverse drug interaction, said Dr. Deepak L. Bhatt of Harvard Medical School and the Veterans Affairs Boston Healthcare System, and his associates in the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT).

“Our trial, in which the study population was at least 10 times as large as those in previous randomized studies and was not selected to represent high-risk patients, showed a significant reduction in clinically manifested gastrointestinal bleeding events, including overt bleeding, with a PPI as compared with placebo,” they noted.

COGENT, an international, randomized, double-blind phase III study, assessed the safety and efficacy of omeprazole in 3,761 patients with coronary heart disease who were already taking clopidogrel plus aspirin. The study subjects were enrolled at 393 sites in 15 countries, randomly assigned to add either omeprazole 20 mg (1,876 patients) or placebo (1,885 patients) to their treatment regimen, and followed for a median of 106 days (341 days maximum). The median age was 69 years in both groups; 67% and 70% of patients were male in the omeprazole and placebo groups, respectively.

The study was halted prematurely when the sponsor, Cogentus Pharmaceuticals, suddenly lost its financial backing; the company has since become defunct. The study’s statistical power is limited because the number of adverse events that developed was smaller than had been anticipated when it was designed.

At 180 days, there were 55 gastrointestinal bleeding events, with 47 patients having 1 such event and 4 patients having 2 events. The GI bleeding event rate was 1.1% with omeprazole, significantly lower than the 2.9% rate with placebo. Similarly, the rates of overt gastroduodenal bleeding, overt upper GI bleeding of unknown origin, and a composite of all overt and occult GI bleeding events also were significantly lower with the active drug.

“The number of patients who would need to be treated for 6 months to prevent one occurrence of an event that was part of the primary gastrointestinal end point was 55, and the number needed to treat to prevent one occurrence of overt GI bleeding was 98,” Dr. Bhatt and his colleagues said (N. Engl. J. Med. 2010 Oct. 6 [doi 10.1056/NEJMoa1007964]).

In addition, at 180 days the percentage of participants with symptoms of gastroesophageal reflux disease was only 0.2% in the omeprazole group, compared with 1.2% in the placebo group.

There were 109 cardiovascular adverse events (55 in the omeprazole group and 54 in the placebo group). The two groups were not significantly different in their rates of the primary cardiovascular end point, a composite of death from CV causes, nonfatal MI, coronary revascularization, or ischemic stroke.

“Although previous observational studies have yielded conflicting results in this regard, [our] study reveals no signal of harm from concomitant clopidogrel and PPI use,” the investigators said.

The rates of serious adverse events did not differ significantly between the two study groups (10% with omeprazole and 9% with placebo). Similarly, the rates of overall diverse events did not differ significantly (41% and 43%, respectively). None of the patients had diarrhea due to Clostridium difficile infection.

This study was supported by Cogentus Pharmaceuticals, which is now defunct. Dr. Bhatt reported receiving grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and the Medicines Company, and his associates reported ties to numerous drug and device manufacturers.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

The use of advanced radiology – CT or MRI imaging – during emergency department visits for injury tripled during a recent decade, according to a report in the Oct. 6 issue of JAMA.

During the same period, there was no increase in the diagnosis of life-threatening conditions or in rates of hospital admission after ED visits, suggesting that the leap in CT and MRI imaging was excessive, yielding no significant benefits to patients, said Dr. Frederick Kofi Korley of the department of emergency medicine, Johns Hopkins University, Baltimore, and his associates.

The investigators used data from the Center for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey to perform what they described as the first study to evaluate national trends in the use of advanced radiology during ED visits for injury-related conditions. The survey details the year-by-year use of ambulatory medical services in a nationally representative sample of approximately 370 general and short-stay hospitals in all 50 states.

Between 1998 and 2007, there were more than 324,000 such visits sampled, including 65,376 (approximately 20%) in which patients had sustained injuries. “This represents an estimated average of 22.4 million visits made to EDs in the United States each year for injury-related conditions,” Dr. Korley and his colleagues said.

Compared with patients who presented to the ED with an injury-related condition in 1998, those who presented in 2007 were approximately three times more likely to undergo CT or MRI. In 1998, advanced radiology imaging was used in 5%-7% of such visits, while in 2007, it was used in 14%-17%. Most of this difference was from an increase in CT rather than MRI.

Yet the percentage of life-threatening conditions in which such imaging would be expected to yield important diagnostic information increased nonsignificantly, from 1.7% to 2.0%, during the same period. Such life-threatening conditions in which CT outperforms x-ray imaging include skull fracture, fracture of the cervical spine, intracranial hemorrhage, laceration of the liver, and laceration of the spleen, the investigators noted.

Moreover, there was no significant change during the study period in the proportion of injury-related ED visits that led to hospital admission (5.9% in 1998 and 5.5% in 2007), nor in the proportion that led to ICU admission (0.62% and 0.80%, respectively).

Patients presenting to academic hospitals were more likely to undergo advanced radiology imaging than were those presenting to nonacademic hospitals. This difference may be because academic hospitals serve more severely injured patients, have less-experienced clinicians (residents) ordering diagnostic tests, or simply have more accessible CT and MRI facilities, Dr. Korley and his associates said (JAMA 2010;304:1465-71).

In patients who underwent CT or MRI imaging, the mean length of ED stay was 126 minutes longer than that for patients who didn’t undergo advanced radiology imaging. This may reflect time spent waiting for imaging to be performed and evaluated by a radiologist, or the fact that patients referred for advanced imaging might be more seriously injured and thus require more intervention than others. Either way, excessive length of ED stay “can contribute to emergency department crowding and can increase the risk of medical error,” the researchers said.

This study was not designed to determine the reason for the large increase in CT and MRI use, but the investigators noted that the increased availability of CT scanners, the routine use of whole-body scanning at some trauma centers, the speed of new-generation CT scanners, patient demand, and concerns about malpractice lawsuits all may have contributed.

No financial conflicts of interest were reported.

A statewide Arizona program that officially endorsed chest-compression-only CPR significantly increased rates of bystander CPR and of patient survival in cases of cardiac arrest, according to a new report in the Oct. 6 issue of JAMA.

“Encouraging a technique that is easier to perform and more acceptable to the public may have helped increase the CPR rate independent of the public education efforts,” said Dr. Bentley J. Bobrow of the Arizona Department of Health Services, Phoenix, and his associates.

Nationally, bystander CPR of any kind is performed in less than 30% of cases. It is thought that bystanders refrain from providing conventional CPR for a variety of reasons, including fear of causing harm, fear of contracting infectious disease, the complexity of the psychomotor task, panic, and reluctance to make mouth-to-mouth contact, they noted.

Beginning in 2005, the investigators conducted a 5-year prospective, observational cohort study to evaluate the effects of implementing the state program, which advocated compression-only CPR through many types of training and information dissemination. “We estimate that at least 30,000 people have been directly trained in the [compression-only] technique and that more than 500,000 were exposed to at least one media forum,” Dr. Bobrow and his colleagues said (JAMA 2010;304:1447-54).

Emergency medical services personnel who responded to calls for out-of-hospital cardiac arrests recorded whether bystanders performed resuscitative measures and which techniques they used. The researchers then assessed outcomes for 4,415 cases that occurred during the next 5 years.

In 2,900 of those cases, there was no bystander CPR. Lay bystanders performed conventional CPR in 666 cases (15%) and compression-only CPR in 849 cases (19%). The overall survival rate was 7%.

After the program was implemented, the rate of lay bystanders performing any type of CPR rose significantly, from 28% at the beginning of the study to 40% at the end of the study period.

The proportion of bystander compression-only CPR attempts rose dramatically, from approximately 20% in 2005 to 76% at the end of 2009, the investigators said.

Survival increased concomitantly, from 3.7% at baseline to 9.8% at the end of the study. Both types of bystander CPR were associated with improved survival, compared with no bystander CPR.

In the subgroup of 1,017 patients with the best prognoses – those whose cardiac arrest was witnessed by a lay bystander and who had a shockable rhythm when the EMS arrived – survival was 17.6% with no CPR and 17.7% with conventional CPR, compared with 33.7% with compression-only CPR.

In addition, survivors attained good neurologic outcomes in 62 of 814 cases with bystander compression-only CPR (7.6%), compared with 34 of 651 cases with bystander conventional CPR (5.2%). That difference was small but significant, Dr. Bobrow and his associates said.

Disclosures: Dr. Cone reported no financial conflicts.

A statewide Arizona program that officially endorsed chest-compression-only CPR significantly increased rates of bystander CPR and of patient survival in cases of cardiac arrest, according to a new report in the Oct. 6 issue of JAMA.

“Encouraging a technique that is easier to perform and more acceptable to the public may have helped increase the CPR rate independent of the public education efforts,” said Dr. Bentley J. Bobrow of the Arizona Department of Health Services, Phoenix, and his associates.

Nationally, bystander CPR of any kind is performed in less than 30% of cases. It is thought that bystanders refrain from providing conventional CPR for a variety of reasons, including fear of causing harm, fear of contracting infectious disease, the complexity of the psychomotor task, panic, and reluctance to make mouth-to-mouth contact, they noted.

Beginning in 2005, the investigators conducted a 5-year prospective, observational cohort study to evaluate the effects of implementing the state program, which advocated compression-only CPR through many types of training and information dissemination. “We estimate that at least 30,000 people have been directly trained in the [compression-only] technique and that more than 500,000 were exposed to at least one media forum,” Dr. Bobrow and his colleagues said (JAMA 2010;304:1447-54).

Emergency medical services personnel who responded to calls for out-of-hospital cardiac arrests recorded whether bystanders performed resuscitative measures and which techniques they used. The researchers then assessed outcomes for 4,415 cases that occurred during the next 5 years.

In 2,900 of those cases, there was no bystander CPR. Lay bystanders performed conventional CPR in 666 cases (15%) and compression-only CPR in 849 cases (19%). The overall survival rate was 7%.

After the program was implemented, the rate of lay bystanders performing any type of CPR rose significantly, from 28% at the beginning of the study to 40% at the end of the study period.

The proportion of bystander compression-only CPR attempts rose dramatically, from approximately 20% in 2005 to 76% at the end of 2009, the investigators said.

Survival increased concomitantly, from 3.7% at baseline to 9.8% at the end of the study. Both types of bystander CPR were associated with improved survival, compared with no bystander CPR.

In the subgroup of 1,017 patients with the best prognoses – those whose cardiac arrest was witnessed by a lay bystander and who had a shockable rhythm when the EMS arrived – survival was 17.6% with no CPR and 17.7% with conventional CPR, compared with 33.7% with compression-only CPR.

In addition, survivors attained good neurologic outcomes in 62 of 814 cases with bystander compression-only CPR (7.6%), compared with 34 of 651 cases with bystander conventional CPR (5.2%). That difference was small but significant, Dr. Bobrow and his associates said.

Disclosures: Dr. Cone reported no financial conflicts.

A statewide Arizona program that officially endorsed chest-compression-only CPR significantly increased rates of bystander CPR and of patient survival in cases of cardiac arrest, according to a new report in the Oct. 6 issue of JAMA.

“Encouraging a technique that is easier to perform and more acceptable to the public may have helped increase the CPR rate independent of the public education efforts,” said Dr. Bentley J. Bobrow of the Arizona Department of Health Services, Phoenix, and his associates.

Nationally, bystander CPR of any kind is performed in less than 30% of cases. It is thought that bystanders refrain from providing conventional CPR for a variety of reasons, including fear of causing harm, fear of contracting infectious disease, the complexity of the psychomotor task, panic, and reluctance to make mouth-to-mouth contact, they noted.

Beginning in 2005, the investigators conducted a 5-year prospective, observational cohort study to evaluate the effects of implementing the state program, which advocated compression-only CPR through many types of training and information dissemination. “We estimate that at least 30,000 people have been directly trained in the [compression-only] technique and that more than 500,000 were exposed to at least one media forum,” Dr. Bobrow and his colleagues said (JAMA 2010;304:1447-54).

Emergency medical services personnel who responded to calls for out-of-hospital cardiac arrests recorded whether bystanders performed resuscitative measures and which techniques they used. The researchers then assessed outcomes for 4,415 cases that occurred during the next 5 years.

In 2,900 of those cases, there was no bystander CPR. Lay bystanders performed conventional CPR in 666 cases (15%) and compression-only CPR in 849 cases (19%). The overall survival rate was 7%.

After the program was implemented, the rate of lay bystanders performing any type of CPR rose significantly, from 28% at the beginning of the study to 40% at the end of the study period.

The proportion of bystander compression-only CPR attempts rose dramatically, from approximately 20% in 2005 to 76% at the end of 2009, the investigators said.

Survival increased concomitantly, from 3.7% at baseline to 9.8% at the end of the study. Both types of bystander CPR were associated with improved survival, compared with no bystander CPR.

In the subgroup of 1,017 patients with the best prognoses – those whose cardiac arrest was witnessed by a lay bystander and who had a shockable rhythm when the EMS arrived – survival was 17.6% with no CPR and 17.7% with conventional CPR, compared with 33.7% with compression-only CPR.

In addition, survivors attained good neurologic outcomes in 62 of 814 cases with bystander compression-only CPR (7.6%), compared with 34 of 651 cases with bystander conventional CPR (5.2%). That difference was small but significant, Dr. Bobrow and his associates said.

Disclosures: Dr. Cone reported no financial conflicts.